OnCo
trialsTrialPositive

COMBI-AD

A year of two targeted pills after surgery halves the risk of relapse in BRAF-mutant melanoma, and the benefit is still visible a decade later.

RFS HR 0.47 at first analysis; final analysis (JCO 2024, >10 years) reported 10-year RFS 48% vs 32% and DMFS 63% vs 48%. OS analysis was hampered by crossover and subsequent immunotherapy. The longest follow-up of any adjuvant melanoma trial; the alternative to adjuvant PD-1 for BRAF-mutant patients.

Setting
Resected stage III BRAF V600-mutant melanoma: adjuvant dabrafenib + trametinib 1 year vs placebo
Phase
Phase 3
Sponsor
Novartis
Registry
Headline result
10-year RFS 48% vs 32%; DMFS 63% vs 48%.
Reported
2017
Enrolled
870
Replication
No second adjuvant BRAF/MEK phase 3 (BRIM8 with vemurafenib alone was mixed); benefit consistent with metastatic COMBI-d/v data.

Outcomes

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In plain words
What these results mean for people, not percentages
870 people took part
Relapse-free survival at 10 yearsprimarysurrogate endpoint
  • 48 vs 32 out of 100 alive without the cancer coming back at 10 years with Dabrafenib + trametinib compared with Placebo; 16 more per 100.
  • Roughly one extra person helped for every 6 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Distant metastasis-free survival at 10 yearssurrogate endpoint
  • 63 vs 48 out of 100 reached this endpoint at 10 years with Dabrafenib + trametinib compared with Placebo; 15 more per 100.
  • Roughly one extra person helped for every 7 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Be careful
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
  • These results apply to the people the trial enrolled: Resected stage III BRAF V600-mutant melanoma: adjuvant dabrafenib + trametinib 1 year vs placebo. People in a different situation may not see the same effect.
  • The trial selected people by a biomarker (BRAF); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

870 participants enrolled.

Relapse-free survival at 10 yearsprimary
Dabrafenib + trametinib48 of 100
Placebo32 of 100
Source
Distant metastasis-free survival at 10 years
Dabrafenib + trametinib63 of 100
Placebo48 of 100
Source
EndpointArmnValueHR (95% CI)pSource
Relapse-free survival at 10 yearsprimaryDabrafenib + trametinib48%link
Placebo32%
Distant metastasis-free survival at 10 yearsDabrafenib + trametinib63%link
Placebo48%
Replication
No second adjuvant BRAF/MEK phase 3 (BRIM8 with vemurafenib alone was mixed); benefit consistent with metastatic COMBI-d/v data.

Connected

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